Thermal ablation and/or hyperthermia are important treatment options for cancer therapy. The possibility of noninvasive thermal techniques for treating cancer is highly medically significant because it reduces the need for complicated and invasive surgery. In addition, it may be possible for a noninvasive technique to treat tumors that are otherwise inoperable through traditional invasive means. High intensity focused ultrasound (HIFU) has been suggested as a possible technique for clinical therapies involving noninvasive thermal ablation or hyperthermia. HIFU allows the targeting of small regions in thermal ablation or hyperthermia treatment. HIFU has been successfully demonstrated in animal models of cancer and in limited clinical studies. However, current noninvasive imaging techniques to stage, monitor, and assess HIFU treatment in vivo are limited in scope and timeliness. If a robust, noninvasive imaging method could be developed to stage, monitor, and assess HIFU treatment, the significance of HIFU to clinical medicine would be greatly enhanced. The long-term objective of the proposed research is to develop and validate a quantitative ultrasound (QUS) model-based imaging technique that will allow the noninvasive staging, monitoring, and assessment of HIFU treatment of tumors in vivo. To accomplish the long-term objective of the proposed research the following specific aims were proposed: 1) Develop a QUS model-based technique to stage and assess the treatment of solid tumors and biological phantoms using HIFU. 2) Develop techniques to monitor HIFU treatment of solid tumors using QUS model-based imaging and coherent backscatter. 3) Evaluate the techniques to stage, monitor, and assess HIFU treatment using simulations and real biological phantoms. 4) Validate the techniques to stage, monitor, and assess HIFU treatment in animal models of cancer. To develop and validate QUS model-based imaging for staging, monitoring, and assessing HIFU treatment of tumors the following plan will be implemented. First, histological analyses of three kinds of tumors from animal models of cancer will be used to construct ultrasonic models of scattering. From these ultrasonic models, QUS parameters expected to yield significant information for classifying and assessing tumors after HIFU treatment will be deduced. Second, detailed measurements and estimates of how these QUS parameters change during treatment will be obtained in order to monitor temperature deposition during treatment. Third, the technique will be optimized and spatial resolution of the QUS model-based imaging determined through simulations and experiments with real biological phantoms undergoing HIFU treatment. Finally, the QUS model-based imaging technique developed through modeling, simulations, and biological phantom experiments will be validated by conducting HIFU treatment on the three animal models of cancer. The ability of QUS model-based imaging to stage, monitor, and assess HIFU treatment in the animal models will be evaluated through comparisons with histology. Public Health Relevance Statement (provided by applicant): High intensity focused ultrasound (HIFU) has been suggested as a possible technique for clinical therapies involving noninvasive thermal ablation or hyperthermia of cancer. Currently, noninvasive imaging techniques to stage, monitor, and assess HIFU treatment in vivo are limited in scope and timeliness, thereby reducing the clinical utility of the approach. In this proposal a quantitative ultrasound (QUS) model based imaging technique will be developed that is sensitive to microstructural changes in tissues and can be used to noninvasively stage, monitor, and assess ultrasound induced hyperthermia or HIFU ablation of tumors in vivo.